Abstract
Objective
To analyze phenotypic classification and other risk factors for interval breast cancer, focusing on true interval and false negative cancers.
Methods
A nested case–control study was performed among 115 cancers detected between two screening mammograms (interval cancers) and 115 screen-detected cancers diagnosed between 1995 and 2008 in a population-based breast cancer screening program in Barcelona (Spain). Bivariate and multivariate analyses were performed to compare patient and tumor molecular characteristics among all interval cancers, true intervals and false negatives, and screen-detected cancers.
Results
A total of 42.5% of interval cancers were true interval tumors and 16.2% were false negatives. High breast density and triple negative phenotype were more frequent in true interval cancers than in screen-detected cancers (57.6 and 34.1%, respectively for breast density, p = 0.023; 28.1 and 7.5%, respectively for triple negative phenotype, p = 0.028), while no statistically significant differences were observed between false negatives and screen-detected cancers. The main adjusted factors associated with true interval cancers compared with screen-detected cancers were high breast density and triple negative phenotype (OR = 3.1, 95% CI, 1.03–9.24 and OR = 8.9, 95% CI, 2.03–38.62, respectively).
Conclusion
A more aggressive molecular phenotype and high breast density were identified in breast tumors that truly arise in the interval between screenings.
Similar content being viewed by others
References
Rakha EA, El Sayed ME, Reis-Filho JS, Ellis IO (2008) Expression profiling technology: its contribution to our understanding of breast cancer. Histopathology 52:67–81
Benson JR, Jatoi I, Keisch M, Esteva FJ, Makris A, Jordan VC (2009) Early breast cancer. Lancet 373:1463–1479
Tornberg S, Codd M, Rodrigues V, Segnan N, Ponti A (2005) Ascertainment and evaluation of interval cancers in population-based mammography screening programmes: a collaborative study in four European centers. J Med Screen 12:43–49
Perry N, Broeders M, de Wolf C, Törnberg C, Holland R, von Karsa L (2006) European guidelines for quality assurance in breast cancer screening and diagnosis, 4th edn. Office for Official Publications of the European Communities, Luxembourg
Vitak B, Olsen KE, Manson JC, Arnesson LG, Stal O (1999) Tumour characteristics and survival in patients with invasive interval breast cancer classified according to mammographic findings at the latest screening: a comparison of true interval and missed interval cancers. Eur Radiol 9:460–469
Brekelmans CT, van Gorp JM, Peeters PH, Collette HJ (1996) Histopathology and growth rate of interval breast carcinoma. Characterization of different subgroups. Cancer 78:1220–1228
Cowan WK, Angus B, Gray JC, Lunt LG, al Tamimi SR (2000) A study of interval breast cancer within the NHS breast screening programme. J Clin Pathol 53:140–146
Porter PL, El Bastawissi AY, Mandelson MT (1999) Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 91:2020–2028
Burrell HC, Sibbering DM, Wilson AR (1996) Screening interval breast cancers: mammographic features and prognosis factors. Radiology 199:811–817
Collett K, Stefansson IM, Eide J (2005) A basal epithelial phenotype is more frequent in interval breast cancers compared with screen detected tumors. Cancer Epidemiol Biomarkers Prev 14:1108–1112
Crosier M, Scott D, Wilson RG, Griffiths CD, May FE, Westley BR (1999) Differences in Ki67 and c-erbB2 expression between screen-detected and true interval breast cancers. Clin Cancer Res 5:2682–2688
Gilliland FD, Joste N, Stauber PM (2000) Biologic characteristics of interval and screen-detected breast cancers. J Natl Cancer Inst 92:743–749
Palka I, Kelemen G, Ormandi K (2008) Tumor characteristics in screen-detected and symptomatic breast cancers. Pathol Oncol Res 14:161–167
Anttinen J, Kuopio T, Nykanen M, Torkkeli H, Saari U, Juhola M (2003) Her-2/neu oncogene amplification and protein over-expression in interval and screen-detected breast cancers. Anticancer Res 23:4213–4218
Irvin WJ Jr, Carey LA (2008) What is triple-negative breast cancer? Eur J Cancer 44:2799–2805
Bare M, Sentis M, Galceran J (2008) Interval breast cancers in a community screening programme: frequency, radiological classification and prognostic factors. Eur J Cancer Prev 17:414–421
Hofvind S, Geller B, Skaane P (2008) Mammographic features and histopathological findings of interval breast cancers. Acta Radiol 49:975–981
Hofvind S, Moller B, Thoresen S, Ursin G (2006) Use of hormone therapy and risk of breast cancer detected at screening and between mammographic screens. Int J Cancer 118:3112–3117
Mandelson MT, Oestreicher N, Porter PL (2000) Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 92:1081–1087
Ciatto S, Visioli C, Paci E, Zappa M (2004) Breast density as a determinant of interval cancer at mammographic screening. Br J Cancer 90:393–396
Porter GJ, Evans AJ, Cornford EJ (2007) Influence of mammographic parenchymal pattern in screening-detected and interval invasive breast cancers on pathologic features, mammographic features, and patient survival. AJR Am J Roentgenol 188:676–683
Boyd NF, Rommens JM, Vogt K (2005) Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol 6:798–808
Harvey JA, Bovbjerg VE (2004) Quantitative assessment of mammographic breast density: relationship with breast cancer risk. Radiology 230:29–41
Li T, Sun L, Miller N (2005) The association of measured breast tissue characteristics with mammographic density and other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 14:343–349
Guo YP, Martin LJ, Hanna W (2001) Growth factors and stromal matrix proteins associated with mammographic densities. Cancer Epidemiol Biomarkers Prev 10:243–248
Pike MC, Pearce CL, Wu AH (2004) Prevention of cancers of the breast, endometrium and ovary. Oncogene 23:6379–6391
Ziv E, Shepherd J, Smith-Bindman R, Kerlikowske K (2003) Mammographic breast density and family history of breast cancer. J Natl Cancer Inst 95:556–558
Kopans DB (2008) Basic physics and doubts about relationship between mammographically determined tissue density and breast cancer risk. Radiology 246:348–353
Nicholson BT, LoRusso AP, Smolkin M, Bovbjerg VE, Petroni GR, Harvey JA (2006) Accuracy of assigned BI-RADS breast density category definitions. Acad Radiol 13:1143–1149
Kavanagh AM, Cawson J, Byrnes GB (2005) Hormone replacement therapy, percent mammographic density, and sensitivity of mammography. Cancer Epidemiol Biomarkers Prev 14:1060–1064
Banks E (2001) Hormone replacement therapy and the sensitivity and specificity of breast cancer screening: a review. J Med Screen 8:29–34
Porter GJ, Evans AJ, Burrell HC, Lee AH, Ellis IO, Chakrabarti J (2006) Interval breast cancers: prognostic features and survival by subtype and time since screening. J Med Screen 13:115–122
Tan DS, Marchio C, Jones RL (2008) Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients. Breast Cancer Res Treat 111:27–44
Dolle JM, Daling JR, White E (2009) Risk factors for triple-negative breast cancer in women under the age of 45 years. Cancer Epidemiol Biomarkers Prev 18:1157–1166
Haffty BG, Yang Q, Reiss M (2006) Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 24:5652–5657
Ma H, Luo J, Press MF, Wang Y, Bernstein L, Ursin G (2009) Is there a difference in the association between percent mammographic density and subtypes of breast cancer? Luminal A and triple-negative breast cancer. Cancer Epidemiol Biomarkers Prev 18:479–485
Ciatto S, Catarzi S, Lamberini MP (2007) Interval breast cancers in screening: the effect of mammography review method on classification. Breast 16:646–652
Acknowledgments
The authors thank Cristina Hernández, Rubén Román, Paco Belvis, and Jose María Velarde for their assistance in analysis and data management and Teresa Baró for technical assistance in performing the immunohistochemical analysis. We also thank the Tumor Bank of the Department of Pathology of Hospital del Mar and Xarxa de Bancs de Tumors de Catalunya for providing tissue samples.
Financial support
This study was partially supported by CIBER de Epidemiología y Salud Pública (CIBERESP) [AE08_004], PS09/01285, RD06/0020/0109 (ISCiii/FEDER) and 2009SRG321 (Generalitat de Catalunya).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Domingo, L., Sala, M., Servitja, S. et al. Phenotypic characterization and risk factors for interval breast cancers in a population-based breast cancer screening program in Barcelona, Spain. Cancer Causes Control 21, 1155–1164 (2010). https://doi.org/10.1007/s10552-010-9541-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-010-9541-6